Plasma cells are the terminally differentiated cells of the B lymphocyte lineage whose sole purpose is to produce antibody molecules. Antibodies are proteins which recognize foreign antigens such as bacterial, viral, or parasitic antigens or toxins, bind them and clear them from the system. Throughout the differentiation process, B lineage cells display cell surface molecules which, in addition to providing specific functions to the B cell, also serve as landmarks for the developmental stage of a B cell or can divide B cells into functional subsets. In an attempt to generate monoclonal antibodies to different subsets of B cells, C57Bl/6 mice were hyperimmunized with DBS/2 spleen cells and hybridomas were produced. Five monoclonal antibodies are currently being analyzed. One monoclonal antibody appears to recognize a MHC class 1 type molecule with cross-reactive specificity. A second monoclonal antibody apeears to recognize an activation antigen on both B and T cells. This molecule is expressed on only a small amount of unactivated B or T cells in the spleen but is found on virtually 100% of B and T lymphocyted when the cells are stimulated with the appropriate antigen. This monoclonal antibody appears to be unique, so far, as it has different profiles from other antibodies which also recognize activation antigens. Further characterisation of this monoclonal antibody and the remaining 3 monoclonals is continuing. The mechanism that produces antibodies is largely understood in that different gene segments are combined to create an antibody with specificity for a particular antigen. The details of the rearrangement process which combines the gene segments are still not understood and the process of "choosing" which gene segments to combine is also not understood. To try to understand these processes, we are studying in detail, a small Vk family, Vk10, which is known to be utilized in a number of different antigenic responses. We have sequenced all members of this 3 gene family and will begin a detailed analysis of the regulatory sequences associated with these genes as well as analysis of the individual gene usage in fetal or newborn and adult mice.